Eric J. Nestler

Eric J. Nestler, M.D., Ph.D., is the Nash Family Professor of Neuroscience, Chairman of the Department of Neuroscience and Director of the Friedman Brain Institute at the Mount Sinai Medical Center in New York.^[1][2] His focus in neuropsychopharmacology concentrates on forming a molecular approach to psychiatry and furthering the understanding of the molecular basis of both depression and drug addiction, using animal models to study the way drug use or stress affects the brain.^[1] His addiction research largely centers around ΔFosB (a master control protein that induces addiction) and associated epigenetic remodeling in the medium spiny neurons of the nucleus accumbens.^[3][4]

Nestler is the author (with Dennis S. Charney) of Neurobiology of Mental Illness (ISBN 0195189809), of Molecular Neuropharmacology (with Steven E. Hyman and Robert C. Malenka; ISBN 978-0-07-148127-4), and more than 450 chapters and peer-reviewed publications.^[5] He is active in seven research projects funded by the National Institute on Drug Abuse and the National Institute of Mental Health.

Biography

Education

Nestler is a graduate of Herricks High School in New Hyde Park, New York. He received his B.A., his Ph.D. and his M.D. from Yale University. He completed his residency in psychiatry at both McLean Hospital in Massachusetts and Yale in 1987.^[1]

Career

Nestler served as the Director of the Division of Molecular Psychiatry at Yale until 2000, and as Chairman of the Department of Psychiatry at the University of Texas Southwestern Medical Center at Dallas.^[1] He joined Mount Sinai in 2008. He has served on the Board of Scientific Counselors of the National Institute on Drug Abuse, on the National Advisory Mental Health Council for the National Institute of Mental Health, the National Advisory Drug Abuse Council for the National Institute on Drug Abuse,^[6] as Council Member of the American College of Neuropsychopharmacology (for which he served as president in 2011) and the Society for Neuroscience. He is a member of the Scientific Advisory Board of the National Alliance for Research in Schizophrenia and Depression (now known as the Brain & Behavior Research Foundation) and of the International Mental Health Research Organization,^[7] as well as a member of the Board of Directors of the McKnight Endowment Fund in Neuroscience.^[8] He was elected to the Institute of Medicine in 1998 and the American Academy of Arts and Sciences in 2005.^[8][9]

Awards

Dr. Nestler's awards and honors include the Pfizer Scholars Award (1987), the Sloan Research Fellowship (1987), the McKnight Scholar Award (1989), the Jordi-Folch-Pi Memorial Award from the American Society of Neurochemistry (1990), the Efron Award of the American College of Neuropsychopharmacology (1994), the Pasarow Foundation Award for Neuropsychiatric Research (1998), the NARSAD Established Investigator Award (1996), the Bristol-Myers Squibb Freedom to Discover Neuroscience Research Grant (2004), the Patricia S. Goldman-Rakic Award and the Falcone Prize both from NARSAD (2008, 2009),^[10] and the Rhoda and Bernard Sarnat International Prize in Mental Health from the Institute of Medicine (2010). He received an honorary doctorate from Uppsala University in Sweden in 2011, and the Anna Monika Prize in Depression Research (2012).^[11][12]

Grants and research

Role	Source, Title	Identifier
Principal Investigator	NIDA, Molecular Neurobiology of Drug Addiction[13]	P01 DA08227
Principal Investigator	NIMH, Pharmacological Actions of Stress & Antidepressants Treatments[14]	R01 MH51399
Principal Investigator	NIDA, Role of Neurotrophic Factors in the Actions of Drugs of Abuse[15]	R01 DA14133
Principal Investigator	NIDA, Molecular Studies of Cocaine Action in Brain[16]	R01 DA07359
Principal Investigator	NIMH, Epigenetic Mechanisms of Depression[17]	P50 MH096890
Principal Investigator	NIMH, Pharmacological Actions of Stress & Antidepressants Treatments	R01 MH51399

Publications (partial list)

• Berton O, McClung CA, DiLeone RJ, Krishnan V, Russo S, Graham D, Tsankova NM, Bolanos CA, Rios M, Monteggia LM, Self DW, Nestler EJ (2006). "Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress". Science 311 (5762): 864–868. doi:10.1126/science.1120972. PMID 16469931.
• Carlezon WA, Boundy VA, Haile CN, Kalb RG, Neve R, Nestler EJ (1997). "Sensitization to morphine induced by viral-mediated gene transfer". Science 277 (5327): 812–814. doi:10.1126/science.277.5327.812. PMID 9242609.
• Carlezon WA, Thome J, Olson VG, Lane-Ladd SB, Brodkin ES, Hiroi N, Duman RS, Neve RL, Nestler EJ (1998). "Regulation of cocaine reward by CREB". Science 282 (5397): 2272–2275. doi:10.1126/science.282.5397.2272. PMID 9856954.
• Colby CR, Whisler K, Steffen C, Nestler EJ, Self DW (2003). "Striatal cell type-specific overexpression of DeltaFosB enhances incentive for cocaine". J. Neurosci 23 (6): 2488–2493. PMID 12657709.
• Feng J, Wilkinson M, Liu X, Purushothaman I, Ferguson D, Vialou V, Maze I, Shao N, Kennedy P, Koo J, Dias C, Laitman B, Stockman V, Laplant Q, Cahill M, Nestler EJ, Shen L (2014). "Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens". Genome Biol 15 (4): R65. doi:10.1186/gb-2014-15-4-r65. PMID 24758366.
• Hyman SE, Malenka RC, Nestler EJ (2006). "Neural mechanisms of addiction: the role of reward-related learning and memory". Annu. Rev. Neurosci 29 (1): 565–598. doi:10.1146/annurev.neuro.29.051605.113009. PMID 16776597.
• Kelz MB, Chen J, Carlezon WA, Whisler K, Gilden L, Beckmann AM, Steffen C, Zhang YJ, Marotti L, Self DW, Tkatch T, Baranauskas G, Surmeier DJ, Neve RL, Duman RS, Picciotto MR, Nestler EJ (1999). "Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine". Nature 401 (6750): 272–276. doi:10.1038/45790. PMID 10499584.
• Kelz MB, Chen JS, Carlezon WA, Whisler K, Gilden L, Beckmann AM, Steffen C, Zhang YJ, Marotti L, Self DW, Tkatch R, Baranauskas G, Surmeier DJ, Neve RL, Duman RS, Picciotto MR, Nestler EJ (1999). "Expression of the transcription factor ∆FosB in the brain controls sensitivity to cocaine". Nature 401 (6750): 272–276. doi:10.1038/45790. PMID 10499584.
• Koo JW, Mazei-Robison MS, Chaudhury D, Juarez B, LaPlant Q, Ferguson D, Feng J, Sun HS, Scobie K, Damez-Werno D, Crumiller M, Ohnishi YN, Ohnishi YH, Mouzon E, Dietz DM, Lobo KM, Neve RL, Russo SJ, Han MH, Nestler EJ (2012). "Novel role of BDNF as a negative modulator of morphine action". Science 338 (6103): 124–128. doi:10.1126/science.1222265. PMID 23042896.
• Krishnan V, Han MH, Graham DL, Berton O, Renthal W, Russo SJ, LaPlant Q, Graham A, Lutter M, Lagace DC, Ghose S, Reister R, Tannous P, Green TA, Neve RL, Chakravarty S, Kumar A, Eisch AJ, Self DW, Lee FS, Tamminga CA, Cooper DC, Gershenfeld HK, Nestler EJ (2007). "Susceptibility and resistance to social defeat are mediated through molecular adaptations in brain reward regions". Cell 131 (2): 391–404. doi:10.1016/j.cell.2007.09.018. PMID 17956738.
• Lobo MK, Covington HE, Chaudhury D, Friedman AK, Sun HS, Damez-Werno D, Dietz D, Zaman S, Koo JW, Kennedy PJ, Mouzon E, Mogri M, Neve RL, Deisseroth K, Han MH, Nestler EJ (2010). "Cell type specific loss of BDNF signaling mimics optogenetic control of cocaine reward". Science 330 (6002): 385–390. doi:10.1126/science.1188472. PMC 3011229. PMID 20947769.
• Maze I, Chaudhury D, Dietz DM, Von Schimmelmann M, Kennedy PJ, Lobo MK, Sillivan SE, Miller ML, Bagot RC, Sun H, Turecki G, Neve RL, Hurd YL, Shen L, Han MH, Schaefer A, Nestler EJ (2014). "G9a influences neuronal subtype specification in striatum". Nature Neuroscience 17 (4): 533–539. doi:10.1038/nn.3670. PMID 24584053.
• Maze I, Covington HE, Dietz DM, LaPlant Q, Renthal W, Russo SJ, Mechanic M, Mouzon E, Neve RL, Haggarty SJ, Ren YH, Sampath SC, Hurd YL, Greengard P, Tarakovsky A, Schaefer A, Nestler EJ (2010). "Essential role of the histone methyltransferase G9a in cocaine-induced plasticity". Science 327 (5962): 213–216. doi:10.1126/science.1179438. PMC 2820240. PMID 20056891.
• McClung CA, Nestler EJ (2003). "Regulation of gene expression and cocaine reward by CREB and ∆FosB". Nature Neuroscience 11 (11): 1208–1215. doi:10.1038/nn1143. PMID 14566342.
• Nestler EJ (2012). "Transcriptional mechanisms of drug addiction". Clin. Psychopharmacol. Neurosci 10 (3): 136–43. doi:10.9758/cpn.2012.10.3.136. PMC 3569166. PMID 23430970.
• Nestler EJ (2008). "Review. Transcriptional mechanisms of addiction: role of DeltaFosB". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 363 (1507): 3245–3255. doi:10.1098/rstb.2008.0067. PMC 2607320. PMID 18640924.
• Nestler EJ, Barrot M, Self DW (2001). "DeltaFosB: a sustained molecular switch for addiction". Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11042–11046. doi:10.1073/pnas.191352698. PMC 58680. PMID 11572966.
• Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM (2013). "Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator". J. Neurosci 33 (8): 3434–42. doi:10.1523/JNEUROSCI.4881-12.2013. PMC 3865508. PMID 23426671.
• Renthal W, Nestler EJ (2009). "Chromatin regulation in drug addiction and depression". Dialogues Clin. Neurosci 11 (3): 257–268. PMC 2834246. PMID 19877494.
• Renthal W, Nestler EJ (2008). "Epigenetic mechanisms in drug addiction". Trends in Molecular Medicine 14 (8): 341–350. doi:10.1016/j.molmed.2008.06.004. PMC 2753378. PMID 18635399.
• Renthal W, Kumar A, Xiao GH, Wilkinson M, Convington HE, Mze I, Sikder D, Robison AJ, LaPlant Q, Dietz DM, Russo SJ, Vialou V, Chakravarty S, Kodadek TJ, Stack A, Kabbaj M, Nestler EJ (2009). "Genome wide analysis of chromatin regulation by cocaine reveals a novel role for sirtuins". Neuron 62 (3): 335–348. doi:10.1016/j.neuron.2009.03.026. PMC 2779727. PMID 19447090.
• Robison AJ, Nestler EJ (2011). "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci 12 (11): 623–637. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194.
• Russo SJ, Bolanos CA, Theobald DE, DeCarolis NA, Renthal WR, Kumar A, Winstanley CA, Renthal NE, Wiley MD, Self DW, Russell DS, Neve RL, Eisch AJ, Nestler EJ (2007). "The IRS2-Akt pathway in midbrain dopaminergic neurons regulates behavioral and cellular responses to opiates". Nature Neuroscience 10 (1): 93–99. doi:10.1038/nn1812. PMID 17143271.
• Sabatakos G, Sims NA, Chen J, Aoki K, Kelz MB, Amling M, Bouali Y, Mukhopadhyay K, Ford K, Nestler EJ, Baron R (2000). "Overexpression of DeltaFosB transcription factor(s) increases bone formation and inhibits adipogenesis". Nature Medicine 6 (9): 985–990. doi:10.1038/79683. PMID 10973317.
• Scobie KN, Damez-Werno D, Sun H, Shao N, Gancarz A, Panganiban CH, Dias C, Koo J, Caiafa P, Kaufman L, Neve RL, Dietz DM, Shen L, Nestler EJ (2014). "Essential role of poly(ADP-ribosyl)ation in cocaine action". Proc Natl Acad Sci USA 111 (5): 2005–10. doi:10.1073/pnas.1319703111. PMID 24449909.
• Self DW, Barnhart WJ, Lehman DA, Nestler EJ (1996). "Opposite modulation of cocaine-seeking behavior by D1-like and D2-like dopamine receptor agonists". Science 271 (5255): 1586–1589. doi:10.1126/science.271.5255.1586. PMID 8599115.
• Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006). "Sustained hippocampal chromatin regulation in hippocampus in a mouse model of depression and antidepressant action". Nature Neuroscience 9 (4): 519–525. doi:10.1038/nn1659. PMID 16501568.
• Vialou V, Robison AJ, LaPlant QC, Covington HE, Dietz DM, Ohnishi YN, Mouzon E, Rush AJ, Watts EL, Wallace DL, Iñiguez SD, Ohnishi YH, Steiner MA, Warren B, Krishnan V, Neve RL, Ghose S, Berton O, Tamminga CA, Nestler EJ (2010). "∆FosB in brain reward circuits mediates resilience to stress and antidepressant responses". Nature Neuroscience 13 (6): 745–752. doi:10.1038/nn.2551. PMC 2895556. PMID 20473292.

References

1. "Mount Sinai Hospital Doctor Profile". Retrieved 9 June 2014.
2. "McGraw Hill Medical". Retrieved 9 June 2014.
3. Whalley K (December 2014). "Psychiatric disorders: a feat of epigenetic engineering". Nat. Rev. Neurosci. 15 (12): 768–769. doi:10.1038/nrn3869. PMID 25409693. Chronic exposure to stress or drugs of abuse causes widespread changes in the activity of chromatin remodelling enzymes. However, it has been difficult to determine the relative functional importance of drug- or stress-induced epigenetic modifications of individual genes. Nestler and colleagues have now employed gene- and brain-region-specific chromatin remodelling to examine the role of one particular gene, [ΔFosB], in addiction- and depression-related changes in the brain and behaviour. ... This study shows that single epigenetic modifications can modulate both [ΔFosB] expression and its behavioural effects. A similar approach may be used to target other genes of interest and elucidate further the changes in molecular pathways that underlie psychiatric disorders.
   ORIGINAL RESEARCH PAPER Heller, E. A. et al. Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. Nature Neurosci. http://dx.doi.org/10.1038/nn.3871 (2014)
4. Dennis S. Charney (2003). "Preface". In Charney, Dennis S. Molecular neurobiology for the clinician. Washington, DC: American Psychiatric Pub. pp. xvi–xvii. ISBN 9781585627332. Dr. Nestler, in Chapter 4, presents an extremely creative and potentially groundbreaking view of the molecular mechanisms and neural circuitry of reward and how they might relate to vulnerability to addictive behaviors. ... Dr. Nestler focuses on two transcription factors, CREB (cAMP response element binding protein) and ΔFosB
5. "PubMed". National Institutes of Health. Retrieved 9 June 2014.
6. "National Institute on Drug Abuse". Retrieved 9 June 2014.
7. "International Mental Health Research Organization". Retrieved 9 June 2014.
8. "The McKnight Endowment Fund for Neuroscience". Retrieved 9 June 2014.
9. "Center for Brain Health". Retrieved 9 June 2014.
10. "NARSAD". Retrieved 9 June 2014.
11. "Max Planck Institute of Psychiatry". Retrieved 9 June 2014.
12. "New York Social Diary". Retrieved 9 June 2014.
13. "NCBI". Am J Addict 10: 201–17. 2001. PMID 11579619.
14. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (December 2000). "NCBI". J. Neurosci. 20: 9104–10. PMID 11124987.
15. "drugabuse.gov". Retrieved 9 June 2014.
16. "Labome". Retrieved 9 June 2014.
17. "NCBI". Annu Rev Pharmacol Toxicol 53: 59–87. 2013. doi:10.1146/annurev-pharmtox-010611-134540. PMID 23020296.

External links

• Nestler Lab at the Icahn School of Medicine